Main Conference - Day 3 (May 14)
Disulfide constrained peptides (DCPs) have gained increased attention as a drug modality due to their exceptional stability and combined advantages of large biologics and small molecules. Chemical synthesis, although widely used to produce DCPs, is associated with high cost both economically and environmentally. To reduce the dependence on solid phase peptide synthesis and the negative environmental footprint associated with it, we present a highly versatile, cost and environmentally friendly bioproduction platform to generate DCPs and their conjugates, as well as chemically modified or isotope labeled DCPs. Using the DCP against the E3 ubiquitin ligase ZNRF3, MK1-3.6.10, as a model peptide, we have demonstrated the use of bacterial expression, combined with Ser ligation, to produce multivalent MK1-3.6.10 and MK1-3.6.10 with N-terminal functional groups. We have also developed a bioproduction method for site-specific incorporation of unnatural amino acids into recombinant DCPs by the amber codon suppression system. Lastly, we produced 15N/13C-labeled MK1-3.6.10 with high yield and assessed the performance of a semi-automated resonance assignment workflow that could be used to accelerate binding studies and structural characterization of DCPs. This study provides a proof of concept to generate functionalized DCPs using bioproduction, providing a potential solution to alleviate the reliance on hazardous chemicals, reduce the cost and expedite the timeline for DCP discovery.
Veranova has developed a proprietary TAG system that enables solution-phase synthesis of biopolymers, including peptides and oligonucleotides. The technology employs a robust tagging strategy to facilitate selective purification and process control, overcoming limitations inherent to solid-phase synthesis. This approach improves scalability, reduces resin dependency, and supports high-purity product generation across diverse sequence lengths and chemistries. The TAG system represents a versatile platform for advancing complex biopolymer manufacturing and accelerating therapeutic innovation.
- Matteo Villain, PhD - Vice President of Peptide and Oligonucleotide, Veranova